Hydrophobic interactions between non-polar groups in aqueous solution play an integral role in many self-organization and aggregation processes, some of which include the folding of proteins to their native states, the formation of supramolecular complexes and biological membranes, and the assembly of surfactant bilayers. Moreover, since the binding affinities of ligands can depend sensitively on hydrophobic forces, understanding the role of water in mediating biomolecular interactions represents one of the most fundamental challenges to drug design and discovery in the post genomic era. Modern theoretical treatments of aqueous solvation suggest that many of the important aspects of hydrophobic interactions can be understood in terms of the properties of bulk water alone. However, an important deficiency of these theories is that they do not directly connect the macroscopic thermodynamic anomalies of water to microscopic hydrogen-bonding interactions and, as a result, the current models inevitably require as inputs some basic information about the structure and thermodynamics of water. The aim of this proposal is to develop a microscopic theory for investigating solvation that does not require the structural and thermodynamic properties of bulk water as an input. The proposed approach is anchored in a relatively simple statistical mechanical foundation that relates the macroscopic behavior of aqueous solutions to the statistical description of their microscopic interactions and structure. Preliminary calculations for bulk water indicate that this approach is promising, as it satisfies a number of stringent tests for reproducing the thermodynamic, structural, and transport properties of bulk water in its liquid, crystalline, and glassy forms.